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ID naloge: 25 Letnik: 1997 Predmet: patologija in histologija
Imunohistološka in citološka analiza ateroskleroticnega procesa v koronarnih arterijah pri difuzni in distalni koronarni bolezni
Avtor: Patricija Mohorko, Bojan Popovic
Mentor: prof. dr. Marjeta Zorc, dr. med., dipl. biol.
IZHODIŠCA: Difuzna in distalna koronarna bolezen je v literaturi opisana kot ateroskleroticni proces, ki ga morfološko karakterizirajo dolgi ateroskleroticni segmenti. Ti difuzno in koncentricno spremenijo strukturo žilne stene vzdolž njenega celotnega poteka Endarteriektomija je kirurška tehnika lušcenja intime in medije prizadete arterije. Poseg pomeni operativno zdravljenje, hkrati pa omogoca tudi raziskavo okvarjene žilne stene.
1. Imunska vaskulama bolezen, ki je opisana v literaturi kot kronicna imunska reakcija po transplantacijah srca, je morfološko podobna ateroskleroticnemu procesu pri difuzni in distalni koronami bolezni. Hipoteza 1: pri difuzni in distalni koronami bolezni pride do imunske reakcije žile, zato pricakujemo da so v steni prisotni mononukleami infiltrati in imunski depoziti. Da bi hipotezo preverili, smo histološko zasledovali prisotnost mononukleamih infiltratov in imunskih depozitov.
2. Iz literature je znano, da so iz arterijske stene izolirali heparin. Heparin je antikoagulantno sredstvo in naj bi bil primama zašcita arterijske stene. Tkivni bazofilci so celice, ki med ostalimi mediatorji izlocajo tudi heparin. Hipoteza 2: pri difuzni in distalni koronami bolezni so spremenjene morfologija, razporeditev in verjemo tudi funkcija tkivnih bazofilcev. Da bi hipotezo preverili, smo histološko analizirali tkivne bazofilce.
3. Najpomembnejši dejavniki tveganja pri nastanku koronarne bolezni so hiperlipoproteinemija, sladkoma bolezen in zvišan krvni pritisk. Hivoteza 3: ucinki razlicnih dejavnikov tveganja se kažejo s specificno morfološko sliko. Poleg tega škodljivo vplivajo na integriteto tkivnih bazofilcev in s tem na njihovo zašcitno antikoagulanmo funkcijo. Da bi hipotezo preverili, smo stereološko analizirali volumsko gostoto mononukleranih infiltratov in numericno gostoto tkivnih bazofilcev pri zgoraj omenjenih dejavnikih tveganja.
MATERIAL IN METODE: V raziskavo smo vkljucili 34 bolnikov, pri katerih je bila z endarteriektomijo odlušcena intima in medija. V stopnicasti seriji rezin smo izvršili histološko, imunofiuorescencno in stereološko analizo. Z imunofiuorescencno analizo smo prikazali v arterijski steni depozite fibrin-fibrinogena ter IgG in IgM depozite. Skupino 34 bolnikov smo z ozirom na dejavnike tveganja razdelili v 6 podskupin. V vsaki smo stereološko izracunali volumsko gostoto mononukleamih infiltratov in numericno gostoto tkivnih bazofilcev.
REZULTATI:
1. Histološka analiza je pokazala intenzivno mononukleamo infiltracijo ter prisotnost imunskih depozitov IgG in IgM v intimi in mediji endarteriektomirane koronarke. 2. Morfološka analiza tkivnih bazofilcev v steni koronark je pokazala vakuolizacijo in degranulacijo teh celic.
3. Volumska gostota mononukleamih infiltratov je bila najvišja pri bolnikih s hiperlipoproteinemijo tipa BI in N, manjša je bila pri bolnikih s hiperlipoproteinemijo tipa Ba in IIb. Pri bolnikih z zvišanim krvnim pritiskom in pri bolnikih s sladkomo boleznijo infiltratov ni bilo. Numericna gostota tkivnih bazofilcev je bila najvišja pri bolnikih z zvišanim krvnim pritiskom in pri bolnikih s hiperlipoproteinemijo tipa Ba in IIb. Pri bolnikih s sladkomo boleznijo in hiperlipoproteinemijo tipa IV so bile vrednosti nižje, najnižje pa so bile pri hiperlipoproteinemiji tipa BI.
ZAKLJUCKI:
1. Imunski depoziti ob mononukleamih infiltatih potrjujejo, da je ateroskleroza pri difuzni in distalni koronami bolezni imunski odgovor na poškodbo v žilni steni.
2. Degranulacija in vakuolinacija tkivnih bazofilcev analiziranih endarteriektomiranih sekvestrov kaže na aktivno udeleženost teh celic v dinamiki razvoja difuzne in distalne koroname bolezni.
3. Prisotnost mononukleamih infiltratov pri hiperlipoproteinemijah v primerjavi s sladkomo boleznijo in zvišanim pritiskom, kjer infiltratov ni bilo, pomeni, da imajo posamezni dejavniki tveganja specificen ucinek na steno krvne žile. Najtežje ateroskleroticne spremembe pri hiperlipoproteinemijah tipa BI in N gre morda pripisati najnižji numericni gostoti tkivnih bazofilcev.
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[Abstract / English version]
Immunohistological and cytological analysis of atherosclerotic process in the diffuse and distal coronary artery disease
Author: Patricija Mohorko, Bojan Popovic
Mentor: prof. dr. Marjeta Zorc, dr. med., dipl. biol.
INTRODUCTION: The diffuse and distal coronary disease is defined as atherosclerotic process which is morphologically characterized by long arteriosclerosis segments. Those segments alter the structure of the vessel wall diffusely and concentrically in the whole course of the vessel. Endarteriectomy is a surgical treatment, but at the same time this technique makes it possible to study the damaged vessel wall.
1. The immune vascular disease, described by literature as a chronic immune reaction after heart transplantations, shows morphologic similarities to the arteriosclerosis process in the diffuse and distal coronary disease. Hypothesis t: In diffuse and distal coronary disease the immune reaction of the vessel is involved and the presence of mononuclear infiltrates and immune deposits in the vessel wall are expected. To confirm this hypothesis, the presence of mononuclear infiltrates and immune deposits were searched histologically.
2. Heparin has reportedly been isolated from the vessel wall. This anticoagulant substance can have the primary role in the protection of the vessel wall. Heparin is one of mediators, secreted by mast cells. Hypothesis 2: Morphology, distribution and probably the function of mast cells are changed in diffuse and distal coronary disease. Mast cells were histologically analysed for this purpose.
3. The hyperlipoproteinemia, diabetes mellitus and hypertension are the most important risk factors for the coronary disease. Hypothesis 3: The effects of each risk factor are reflected in a specific morphology of the vessel wall. Apart from that, risk factors affect the integrity and the protective anticoagulant function of mast cells. In order to verify this hypothesis, the volume density of mononuclear infiltrates and the numeric density of mast cells were stereologically analysed for each above mentioned risk factor.
MATERIALS AND METHODS: 34 patients who underwent endarteriectomy procedure of tunica intima and media were investigated. Histologic, immunofluorescent and stereologic analysis were performed in the step serial sections. The immunofluorescent analysis showed the deposits of fibrin-fibrinogen, and IgG and IgM deposits. Regarding risk factors, the group of 34 patients was divided into 6 subgroups. In each group the volume density of mononuclear infiltrates and numeric density of mast cells were stereologically evaluated.
RESULTS:
1. By the use of the histologic analysis, an intensive mononuclear infiltration and the presence of fibrin fibrinogen, IgG and IgM deposits in tunica intima and media of the endarteriectomized coronary vessel were found.
2. The morphologic analysis of mast cells showed their vacuolination and degranulation.
3. The highest volume density of mononuclear infiltrates appeared in patients with hyperlipoproteinemias type BI and N Lower levels were found in hyperlipoproteinemias type Ba and IIb. There were no infiltrates in patients with diabetes mellitus. The highest numeric density of mast cells was found in patients with hypertension and hyperlipoproteinemias type Ba and IIb. Lower levels were found with diabetes mellitus and hyperlipoproteinemia type N, with the lowest level in patients with hyperlipoproteinemia type BI.
CONCLUSIONS:
1. The immune deposits, accompanying mononuclear infiltrates prove the hypothesis that atherosclerosis in difuse and distal coronary disease is an immme response to the damage of the vessel wall.
2. Degranulation and vacuolnation of mast cells in endarteriectomized sequestres indicate the active role of those cells in the development dynamics of ditFuse and distal coronary disease.
3. The presence of mononuclear infiltrates with hyperlipoproteinemias, compared to diabetes mellitus and hypertension where no infiltrates were found, proves the fact that each risk factor affects the vessel wall specifically. The lowest numeric density of the mast cells might be the reason for the worst atherosclerotic changes which occur in hyperlipoproteinemias type BI and N.
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